Wasteosomes (corpora amylacea) of the human brain accumulate in CD44-positive astrocytes

Wasteosomes or corpora amylacea are polyglucosan inclusions that accumulate in the human central nervous system during aging and in several neurodegenerative diseases. They are formed in astrocytes, act as waste containers, and can be released into the cerebrospinal fluid. In the present study, we hypothesized that CD44-positive astrocytes are the cells that harbor these structures. Brain tissue samples from non-diseased and diseased cases were analyzed by immunohistochemistry and immunofluorescence. Across multiple brain regions, wasteosomes were exclusively found in areas where astrocytes were CD44-positive. Notably, GFAP-positive astrocytic filaments are observed between the wasteosomes and the CD44 membrane receptor, supporting that the wasteosome-containing astrocytes are CD44-positive. In addition, some wasteosomes observed in the subarachnoid space contained CD44 remnants adhered to their surface. These findings identify CD44-positive astrocytes as the principal cellular niche for wasteosomes. The possible roles of CD44 in wasteosome biogenesis and release are discussed, opening the way for future studies.